PREDICTION AND MANAGEMENT OF

SEVERE DENGUE

LEONARD NAINGGOLAN

Division of Tropical Infectious Disease

Departement of Internal Medicine

FMUI-CM Hospital

Virulence and viral load

ADE

Innate immunity

T-cell-mediated

Complement

Autoimmune disease

Apoptosis

Cytokine Tsunami

Genetic

Immune system

Liver

Vascular Endothelium

Lei HY et al. Immunopathogenesis of Dengue infection. J Biomed 2001

Hematocrit ↑

→→→

Petekie

I had high fever from 6 days ago.

So I went to a hospital at the first day of fever

Case 1.

DAY -7 -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 10 11 12

Bite

I had high fever from 6 days ago.

So I went to a hospital at the first day of fever

They tested Dengue IgG/IgM.

Case 1.

DAY -7 -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 10 11 12

Bite

I had high fever from 6 days ago.

So I went to a hospital at the first day of fever

They tested Dengue IgG/IgM.

IgM/IgG Dengue (-)

Case 1.

DAY -7 -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 10 11 12

Bite

Dr. said it is not dengue fever!!

Case 2.

DAY -7 -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 10 11 12

Bite

I had high fever from 6 days ago.

So I just took a aspirin.

But I could not get over, so I visit hospital this morning.

Case 2.

DAY -7 -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 10 11 12

Bite

I had high fever from 6 days ago.

So I just took a aspirin.

But I could not get over, so I visit hospital this morning.

They tested Dengue NS1 Ag.

Case 2.

DAY -7 -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 10 11 12

Bite

I had high fever from 6 days ago.

So I just took a aspirin.

But I could not get over, so I visit hospital this morning.

They tested Dengue NS1 Ag.

Dengue NS1 Ag (-)

Dr. said it is not dengue fever!!

VIRUS DENGUE

Ag/A

b level

Day

IgMIgG

Immune Response

Symptom

NS1 Ag

DAY -7 -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 10 11 12

AntibodyBite

NS1 Ag

CRITICAL PHASE

CONVALESENCE PHASEACUTEPHASE

█ Response to Primary Infection

1. NS1 antigens

Day 1 after onset of fever and up to Day 9.

Not detectable once anti-NS1 IgG antibodies are produced.

2. IgM antibodies

Day 5 after onset of fever and rise

for 1-3 weeks, then for up to 60 days.

3. IgG antibodies

Day 14 after onset of fever and persists for life.

Dengue Markers

█ Response to Secondary Infection

1. NS1 antigens

Day 1 after onset of fever and up to Day 9.

Not detectable once anti-NS1 IgG antibodies are produced

(Appearance in short period )

2. IgM antibodies

Produced at low or undetectable levels or

for a shorter period than in a primary infection.

3. IgG antibodies

Rise rapidly 1-2 days after onset of symptoms.

Dengue Markers

MENGHITUNG HARI DEMAM

• Tn A, 25 thn datang dg demammendadak tinggi sejak 2 hari yll. Selain demam, pasien jugamengeluh pegal2, atralgia. Tetangga pasien ada yg dirawat krnDBD.

• Tn Z, 32 thn datang dg demammendadak tinggi sejak 5 hari yll. Selain demam, pasien jugamengeluh pegal2, atralgia. Tetangga pasien ada yg dirawat krnDBD.

Faktor prediktor Koef SE z p> |z| IK 95%Skor

Petekie (+) 0,439 0,360 1,22 0,222 -0,266 – 1,144 14

Trombosit < 134.000 ( /µL) 0,034 0,013 2,68 0,007 0,009– 0,059 31

SGOT ≥ 48 (U / L) 0,311 0,367 0,85 0,396 -0,408 – 1,030 10

MODEL PREDIKSI KEBOCORAN PLASMA PADA PENDERITA INFEKSI DENGUE DENGAN DEMAM ≤ 48 JAM

Jumlah skor Tindakan

< 24 Rawat jalan

≥ 24 Rawat inap dan pemberian cairan

infus

Pleural-Effusion Index (PEI)

• PEI at time of admission had the most critical role to predict shock in DHF

• PEI > 6% at time of admission had significant correlations with the occurance of shock

(Tatty ,2004 )

• An ideal, safety, noninvasive investigation to detect plasma leakage (pleural - pericardial effusion & ascites), hepatomegaly, splenomegaly.

• Abdominal & chest scanning

ULTRASONOGRAPHY

• GB-wall-thickening wall thickness > 3 mm

• Pericholecystic fluid

• Minimal ascites

• Pleural & pericardial effusion

• Hepatosplenomegaly

Detect the early mild form of DHF

A. THE EVALUATION OF THE GALL BLADDER SHOULD BE DONE PREPRANDIALLY.THE NORMAL THICKNESS OF GB WALL SHOULD NOT EXCEED 3 MM.

B & C. SAGITAL & TRANSVERSE IMAGES OF HYPOALBUMINEMIA SHOW MARKED THICKENING OF THE GALLBLADDER WALL WITH A SMALL LUMEN.

A B C

• Fluids in the perirenal & pararenal region

• Hepatic & splenic subcapsular fluid

• Pancreatic enlargement

Detect The Severe Form of DHF :

ULTRASONOGRAPHY

TATALAKSANA

• Setelah diperiksa pada Tn A ditemukan keadaan umumbaik, hemodinamik baik, dapat makan dan minum denganbaik. Mual, muntah, dan mimisan disangkal.

• Hasil pemeriksaan laboratorium menunjukkan Leukosit4800/mm3, Hematokrit 40 vol%, Trombosit 251000/mm3.

• Diinfus?

• Dirawat?

• ???

TATALAKSANA

• Setelah diperiksa pada Tn Z ditemukan mual, muntah, dan mimisan.

• Hasil pemeriksaan laboratorium menunjukkan Leukosit1900/mm3, Hematokrit 43 vol%, Trombosit 59000/mm3.

• Diinfus?

• Dirawat?

• ???

Suspect DHFSpontaneous and Massive Bleeding( - )

Shock (-)

- Hb, Ht (n)- Platelets< 100.000- Crystalloid infusion *- Hb, Ht, Plt every 24 hours

- Hb, Ht increase 10-20%- Platelets< 100.000- Crystalloid Infusion *- Hb, Ht, Plt every 12 hours **

- Hb, Ht increase > 20%- Platelets< 100.000

Protocol – Fluid ReplacementDHF with increased Ht > 20%

* Daily crystalloid volume required:

According to formula : 1500 + 20 x (body weight in kg - 20)

Example of calculation for body weight of 55 kg : 1500 + 20 x (55-20) = 2200 ml

(Pan American Health Organization:

Dengue and Dengue Hemorrhagic Fever: Guidelines for Prevention and Control.

PAHO: Washington, D.C., 1994: 67).

** Monitoring is adjusted with phase/day of disease development and symptoms

FLUID REPLACEMENT ON PROBABLE DENGUE

INFECTION IN WARDS

MANAGEMENT OF DHF WITH INCREASE OF

HAEMATOCRITE >20%

MANAGEMENT OF DENGUE SHOCK SYNDROME

Airway

Breathing : O2 1-2 L/min with nasal cannuls, higher use a simple mask

Circulation : crystalloid / colloid 10-20 mL/kg BW loading (If possible less than 10

min) . Evaluate BP, PP, pulse & diuresis.

Response*

Not Response Not Response, shock still happen

Response

Crystalloid 7 mL/kg BW in 1 h

Crystalloid 5 mL/kg BW in 1 h

Consider for nutrition after 12

h (Dx 5 % If no

contraindication)

Within 24-48 h after shock controlled,

vital signs/Ht stable, urine output

increasing

Crystalloid 20-30 mL/kg BW loading for 20-30 min

Not Response

Ht increase Ht decrease

Colloid 10-20 mL/kg BW loading for 10-15 min Blood transfusion 10 mL/kg

BW can be repeated if

necessary

Not ResponseResponse*

Colloid until max 30 mL/kg BW

Not ResponseResponse*

CVPStop infusion

Response

Crystalloid 3 mL/kg BW in 1 h

Response

CVP

Colloid, if max dose does not reached yet or

crystalloid/gelatin (if colloid have reached max dose)

10 mL/kgBW in 10 min, can be repeated until 30

mL/kgBW ; CVP target 15-18 cmH2O

Hypovolemic Normovolemic

Monitoring

crystalloid for

10-15 min

Not Response

Acid-base &

electrolyte

disturbance,

hypoglycemia

, anemia,

secondary

infection

correction

Inotropic,

Vasopressor,

drug

Vasopressor

gradual

increment

Colloid &

crystalloid

combination

Response*

Response:

1. Systolic BP 100 mmHg

2. PP > 20 mmHg

3. Heart Rate < 100 x/mnt, adequate vol

4. Warm extremities

5. Diuresis 0,5-1 cc/kgBW/hour

(CONTINUED)

MANAGEMENT OF DENGUE SHOCK SYNDROME

THANK YOU